Precise Transplantation of Human Amniotic Epithelial Stem Cells Into Lateral Ventricle for Parkinson's Disease

This is a single-center, single-arm, dose escalation study, to explore the safety, tolerability and efficacy of human amniotic epithelial stem cells (hAESCs) for idiopathic Parkinson's disease (PD).

Study Overview

• Status: Recruiting
• Conditions: Idiopathic Parkinson's Disease
• Intervention / Treatment: Biological: hAESCs

Detailed Description

hAESCs will be administration through the Ommaya reservoir implanted into the lateral ventricle of subjects with idiopathic PD.

This dose escalation will be followed by an exploratory expansion phase in 3 cohorts.

• Dose A (5×10^7 cells/dose)
• Dose B (1.0×10^8 cells/dose)
• Dose C (1.5×10^8 cells/dose).

• Study Type: Interventional
• Enrollment (Anticipated): 18
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Jingwen Wu, M.D.; Phone Number: 021-38804518; Email: wujingwendongfang@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200000
      • Recruiting
      • Shanghai East Hospital
      • Contact: Jingwen Wu, M.D.; Phone Number: 18916111526; Email: wujingwendongfang@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 40-70 years old, with more than 5 years of idiopathic PD history
2. UPDRS-III off-time scores ≤49
3. MMSE scores ≥24
4. HAMD-17 scores < 25
5. H-Y on-time scores ≤4
6. reactive to levodopa or dopa agonists
7. PD medication dose is stable for more than 2 months
8. no general anesthesia contraindications, no stereotactic surgery contraindications or other conditions that interfere with clinical evaluation
9. no abnormalities affecting cell transplantation by cranial MRI
10. no participation of other clinical trials 3 months before signing the informed consent

Exclusion Criteria:

1. secondary PD or Parkinson's syndrome
2. subcutaneous apomorphine treatment
3. scoring ≥ 2 on UPDRS-I item 2, or ≥ 2 on UPDRS-II item 13; or ≥ 3 on UPDRS-II item14
4. history of intracranial surgery or device implantation, including deep brain stimulation, within 2 years prior to signing informed consent
5. history of seizures or prophylactic application of antiepileptic drugs
6. other serious central nervous system disorders
7. history of stem cell therapy
8. subject who had undergone a major surgery within 3 months and will undergo a major surgery within the next 6 months prior to signing informed consent
9. autoimmune disease or current use of Immunosuppressants
10. subjects with comorbid cardiac disease, for example, but not limited to, ischemic heart disease, congestive heart failure, significant arrhythmias or cardiac conduction block
11. poorly controlled hypertension, diabetes mellitus, or comorbid endocrine system disorders, pulmonary disorders, gastrointestinal system disorders, serious infections, malignancies, etc.
12. positive for hepatitis B surface antigen (HBsAg), hepatitis C virus (HCV) antibodies, human immunodeficiency virus (HIV) antibodies, or Treponema pallidum antibody
13. abnormalities in liver or kidney function tests, including alanine aminotransferase (ALT), aspartate aminotransferase (AST) is less than 2.5 times the upper limit of normal, blood urea nitrogen (BUN) or creatinine(Cr) are less than 1.5 times the upper limit of normal, or serum albumin < 30.0 g/L
14. abnormalities in hematologic test: coagulation disorders or ongoing anticoagulation therapy; moderate to severe anemia; platelet count < 80 × 10^9/L
15. inability to undergo MRI and positron emission tomography (PET) examinations
16. subject with severe allergies
17. women of childbearing potential (WOCBP) or subject is a man with a WOCBP partner, who are unwilling to take contraception during the trial
18. pregnant or lactating females
19. other conditions deemed by the investigator to be inappropriate for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: hAESCs treatment; hAESCs will be administration through Ommaya reservoir implanted into the lateral ventricle. The tolerability, safety, and efficacy will be examined of 4 monthly doses of hAESCs for 3 months followed by 2 doses every 3 months in dose escalation through 3 cohorts.; Dose A (5×10^7 cells/dose); Dose B (1.0×10^8 cells/dose); Dose C (1.5×10^8 cells/dose).	Biological: hAESCs; human Amniotic Epithelial Stem Cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose limiting toxicity (DLT)	The occurrence of DLT.	12 months
Number of participants with adverse event (AE), serious adverse event(SAE) and adverse events of special interest (AESI)	According to CTCAE V5.0, AE, SAE and AESI evaluated by laboratory examination, measurement of vital signs, physical examination, and subjects' symptoms to detect new abnormalities and/or deterioration of previous conditions. AESI is defined as intracranial infection, hemorrhage, rejection, edema, as well as acute allergic reactions and ectopic mass formation associated with the therapy.	12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the UPDRS-III (Unified Parkinson's Rating Scale part III/motor part) scores	UPDRS is used for evaluating the impairment and disability associated with PD. It consists of 4 sections: I Mentation, behavior, and mood; II Activities of daily living (ADLs); III Motor; and IV Complications.The UPDRS score ranges from 0 to 199, with higher score indicating greater disability	12 months
Change from baseline in the UPDRS off-time total scores	UPDRS is used for evaluating the impairment and disability associated with PD. It consists of 4 sections: I Mentation, behavior, and mood; II Activities of daily living (ADLs); III Motor; and IV Complications.The UPDRS score ranges from 0 to 199, with higher score indicating greater disability	12 months
Change from baseline in the UPDRS on-time total scores	UPDRS is used for evaluating the impairment and disability associated with PD. It consists of 4 sections: I Mentation, behavior, and mood; II Activities of daily living (ADLs); III Motor; and IV Complications.The UPDRS score ranges from 0 to 199, with higher score indicating greater disability	12 months
Change from baseline in sum of the UPDRS-II and UPDRS-III scores	UPDRS is used for evaluating the impairment and disability associated with PD. It consists of 4 sections: I Mentation, behavior, and mood; II Activities of daily living (ADLs); III Motor; and IV Complications.The UPDRS score ranges from 0 to 199, with higher score indicating greater disability	12 months
Changes from baseline in the Parkinson's Disease Questionnaire (PDQ-39) scores	The PDQ-39 is a self-completed questionnaire assessing how often people with Parkinson's experience difficulties across 8 dimensions of daily living with 39 questions . Questions are answered using a 5-point ordinal scoring system: 0 = never, 1 = occasionally, 2 = sometimes, 3 = often, 4 = always. Each scores range from 0 = never have difficulty to 100 = always have difficulty.The higher the score, the lower the quality of life of PD patients.	12 months
Changes in the Hamilton Depression-17 (HAMD-17) Scale scores	The HAMD-17 Scale is the most widely used scale in clinical evaluation of depression in PD patients. This project takes 8 points as the critical value of depression, and the total score over 35 points is considered as severe depression, more than 20 points is likely to be diagnosed with depression, less than 8 points is not depressed.	12 months
Change from baseline in the Parkinson's Disease Sleep Scale (PDSS) scores	The PDSS is a visual analogue scale addressing 15 commonly reported symptoms associated with sleep disturbance overall quality of night's sleep (item 1), sleep onset and maintenance insomnia (items 2 and 3), nocturnal restlessness (items 4 and 5), nocturnal psychosis (items 6 and 7), nocturia (items 8 and 9), nocturnal motor symptoms (items 10-13), sleep refreshment (item 14) and daytime dozing (item 15). Scores range from 0 (poorly or often) to 10 (very good or never), with a total score of <90 indicating sleep disturbance, with higher scores indicating better sleep quality.	12 months
Changes from baseline in the Hoehn and Yahr scale (H-Y)	The Hoehn and Yahr scale is used to provide a general estimate of clinical function of PD patients, combining functional deficits (disability) and objective signs (impairment). The Hoehn and Yahr score ranges from 0 to 5, with higher score indicating higher dysfunction of PD patients.	12 months
Changes from baseline in the Mini-Mental State Examination (MMSE)	The total score of tne MMSE ranges from 0 to 30, with a higher score indicating better function for Cognitive assessment.	12 months

Collaborators and Investigators

• Sponsor: Shanghai East Hospital
• Collaborators: Shanghai iCELL Biotechnology Co., Ltd, Shanghai, China
• Investigators: Principal Investigator: Jingwen Wu, M.D., Shanghai East Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2023
• Primary Completion (Anticipated): February 1, 2025
• Study Completion (Anticipated): February 1, 2026

Study Registration Dates

• First Submitted: January 10, 2023
• First Submitted That Met QC Criteria: January 10, 2023
• First Posted (Actual): January 19, 2023

Study Record Updates

• Last Update Posted (Actual): February 17, 2023
• Last Update Submitted That Met QC Criteria: February 16, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: SA-HAES-102

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No